Physical activity attitudes, intentions and behaviour among 18-25 year olds: a mixed method study

Peer reviewedPublisher PD

A systematic review and narrative synthesis of footwear and orthotic devices used in the management of ankle haemarthrosis and haemarthropathy in haemophilia

Introduction Haemarthrosis is a clinical feature of haemophilia leading to haemarthropathy. The ankle joint is most commonly affected, resulting in significant pain, disability and a reduction in health-related quality of life. Footwear and orthotic devices are effective in other diseases that affect the foot and ankle, such as rheumatoid arthritis, but little is known about their effect in haemophilia. Aims To review the efficacy and effectiveness of footwear and orthotic devices in the management of ankle joint haemarthrosis and haemarthropathy in haemophilia. Methods A systematic literature review was conducted. Two review authors independently screened studies for inclusion and appraised methodological quality using Joanna Briggs Institute Critical Appraisal checklists. A narrative analysis was undertaken. Results Ten studies involving 271 male participants were eligible for inclusion. All studies were quasi-experimental; three employed a within-subject design. Two studies included an independent comparison or control group. A range of footwear and orthotic devices were investigated. Limited evidence from non-randomised studies suggested that footwear and orthotic devices improve the number of ankle joint bleeding episodes, gait parameters, and patient-reported pain. Conclusion This review demonstrates a lack of robust evidence regarding the efficacy and effectiveness of footwear and orthotic devices in the management of ankle joint haemarthrosis and haemarthropathy in haemophilia. Methodological heterogeneities and limitations with the study designs, small sample sizes and limited follow-up of participants exist. Future studies utilising randomised designs, larger sample sizes, long-term follow-up, and validated patient-reported outcome measures are needed to inform the clinical management of ankle joint haemarthrosis and haemarthropathy

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Friendship as a Political Concept: A Groundwork for Analysis

What kind of a concept is friendship, and what is its connection to politics? Critics sometimes claim that friendship does not have a role to play in the study of politics. Such objections misconstrue the nature of the concept of friendship and its relation to politics. In response, this article proposes three approaches to understanding the concept of friendship: (1) as a ‘family resemblance’ concept, (2) as an instance of an ‘essentially contested’ concept, and (3) as a concept indicating a problématique. The article thus responds to the dismissal of friendship by undertaking the groundwork for understanding what kind of a concept friendship might be, and how it might serve different purposes. In doing so, it opens the way for understanding friendship’s relation to politics

A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

Galaxy and Mass Assembly (GAMA): Accurate number densities and environments of massive ultracompact galaxies at 0.02 < z < 0.3

Massive Ultracompact Galaxies (MUGs) are common at z=2-3, but very rare in the nearby Universe. Simulations predict that the few surviving MUGs should reside in galaxy clusters, whose large relative velocities prevent them from merging, thus maintaining their original properties (namely stellar populations, masses, sizes and dynamical state). We take advantage of the high-completeness, large-area spectroscopic GAMA survey, complementing it with deeper imaging from the KiDS and VIKING surveys. We find a set of 22 bona-fide MUGs, defined as having high stellar mass (>8x10^10 M_Sun) and compact size (R_e ~ 10^10 M_Sun Kpc^-2). Interestingly, a large fraction feature close companions -- at least in projection -- suggesting that many (but not all) live in the central regions of groups. Halo masses show these galaxies inhabit average-mass groups. As MUGs are found to be almost equally distributed among environments of different masses, their relative fraction is higher in more massive overdensities, matching the expectations that some of these galaxies fell in these regions at early times. However, there must be another channel leading some of these galaxies to an abnormally low merger history because our sample shows a number of objects that do not inhabit particularly dense environments. (abridged

The Equifinality of Archaeological Networks: an Agent-Based Exploratory Lab Approach

When we find an archaeological network, how can we explore the necessary versus contingent processes at play in the formation of that archaeological network? Given a set of circumstances or processes, what other possible network shapes could have emerged? This is the problem of equifinality, where many different means could potentially arrive at the same end result: the networks that we observe. This paper outlines how agent-based modelling can be used as a laboratory for exploring different processes of archaeological network formation. We begin by describing our best guess about how the (ancient) world worked, given our target materials (here, the networks of production and patronage surrounding the Roman brick industry in the hinterland of Rome). We then develop an agent-based model of the Roman extractive economy which generates different kinds of networks under various assumptions about how that economy works. The rules of the simulation are built upon the work of Bang (2006; 2008) who describes a model of the Roman economy which he calls the ‘imperial Bazaar’. The agents are allowed to interact, and the investigators compare the kinds of networks this description generates over an entire landscape of economic possibilities. By rigorously exploring this landscape, and comparing the resultant networks with those observed in the archaeological materials, the investigators will be able to employ the principle of equifinality to work out the representativeness of the archaeological network and thus the underlying processes

Renal cancer associated with recurrent spontaneous pneumothorax in Birt-Hogg-Dubé syndrome: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Birt-Hogg-Dubé syndrome is a rare genodermatosis characterized by hair follicle hamartomas, renal tumors and spontaneous pneumothorax. We present the case of a patient with pulmonary cysts and recurrent spontaneous pneumothorax. She had typical skin lesions, and was found to have a hybrid oncocytoma which was surgically excised.</p> <p>Case presentation</p> <p>A 60-year-old Caucasian woman had a 10-year history of cystic lung disease and recurrent spontaneous pneumothoraces. She was noted to have papular lesions over her face and forehead. The result of a biopsy showed these lesions to be fibrofolliculomas. A diagnosis of Birt-Hogg-Dubé syndrome was made and she was screened for renal tumors since these are a recognized association. A hybrid oncocytoma was detected which was surgically excised by partial nephrectomy.</p> <p>Conclusion</p> <p>It is important to consider a possible diagnosis of Birt-Hogg-Dubé syndrome in cases of recurrent pneumothorax. Affected individuals must be screened for renal tumors, a potentially lethal consequence of this syndrome.</p